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Adv. Immunology > Gout and Hyperuricemia > Flashcards

Gout and Hyperuricemia Flashcards

1
Q

Gout

A

Common form of severe, painful inflammatory arthritis that presents in an acute attack or flare

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2
Q

How is gout characterized by?

A
  • Elevated serum urate
  • Monosodium urate (MSU) crystals deposits in joints, bones, and/or soft tissue
  • Crystal induced inflammation
    • Acute intermittent episodes of synovitis with joint swelling and pain, called gouty arthritis, gout attacks, or acute gout flares
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3
Q

What are some non-modifiable risk factors of gout?

A

i. Male gender
ii. Elderly
iii. Living in developed countries
iv. Genetics

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4
Q

What are some modifiable risk factors of gout?

A
  • Diet high in purine
  • High fructose corn syrup
  • Alcohol (beer and wine)
  • Medications
  • Obesity
  • Disease statements: HTN, HLD, and CKD
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5
Q

What are some things that lead to overproduction of uric acid?

A
  • Diet
  • Medications
    • Cytotoxic agents
    • Losartan increases uric acid excretion
  • Conditions associated with hyperuricemia
    • Psoriasis
    • Sickle cell anemia
    • Lympho-/myeloproliferative disorders
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6
Q

What are some things that could lead to underexcretion of uric acid?

A
  • Renal impairment
  • HTN
  • Alcohol
  • Medications
    • Thiazides
    • Loop
    • Levodopa
    • Low-dose aspirin (<325 mg)
    • Tacrolimus/cyclosporine
  • Dehydration
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7
Q

How do you diagnose gout?

A
  • Aspiration of synovial fluid or tophi
    • Gold standard
    • Definitive diagnosis
  • Blood test
    • Serum uric > 6.5-6.8 mg/dL
    • Use of hyperuricemia may be difficult during an initial acute attack
    • Best time to check uric level 2 weeks after a flare
  • Diagnosis based on symptoms
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8
Q

What are the clinical presentation of gout?

A
  • Usually presents as an acute flare
  • Intense joint pain that comes suddenly, often in the middle of the night
  • Joints are swollen, painful, red, and warm to touch
  • Most commonly affects the big toe; can occur in other toe joints, ankle, knee and more
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8
Q

Tophi

A
  • Visible or palpable soft tissue masses
  • Asymptomatic nodules or lesions
  • White or yellow deposits
  • Overlying skin pulled taut
  • Long term built up uric acid over time
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9
Q

What are the four stages of gout?

A
  • Asymptomatic
  • Acute gouty arthritis
  • Intercritical gout
  • Chronic gout
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10
Q

Asymptomatic gout

A
  • Serum uric acid level ≥ 6.8 mg/dL
  • No history of previous gouty attack
  • No physical or clinical manifestations
  • May never experience an attack
  • This stage generally DOES NOT warrant treatment; reserve treatment for clinical gout
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11
Q

What is the onset of acute gouty attacks?

A

abrupt release of urate crystals into joint space

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12
Q

What are the symptoms of acute gouty attacks?

A
  • Severe pain
  • Redness
  • Swelling
  • Possibly systemic symptoms such as a fever
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13
Q

Intercritical gout

A
  • Asymptomatic period between attacks
  • Patients may experience
    • Persistent urate crystals in joint
    • Low-grade chronic inflammation
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14
Q

Chronic gout

A

i. Presence of tophi, persistent joint stiffness and inflammation, or radiographic erosions
ii. Result of frequent recurrences and continued accumulation of deposits leading to erosion
iii. Usually takes many years to develop

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15
Q

What are some complications of gout?

A

i. Joint damage and deformity
ii. Kidney stones
iii. Kidney disease and kidney failure
iv. Psychological and emotional problems

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16
Q

Acute gout attacks

A
  • Initiate pharmacologic treatment within 24 hours of onset of an acute gout attack
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17
Q

What are the first line agents for gout flares?

A
  • NSAIDs
  • Colchicine
  • Steroids
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18
Q

What is the boxed warning for NSAIDs?

A

Increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI), and stroke

19
Q

What are some gastrointestinal effects of NSAIDs?

A
  1. Dyspepsia
  2. Gastroduodenal ulcers
  3. GI bleeding and perforation
20
Q

What are some cardiovascular effects of NSAIDs?

A
  1. MI
  2. Stroke and thrombotic events
  3. CHF
  4. Edema
  5. Hypertension
21
Q

What is the neprotoxicity side effects for gout?

A
  1. Electrolyte imbalance
  2. Edema
  3. Reduced eGR
  4. Acute interstitial nephritis
  5. Chronic kidney disease
22
Q

Who should you avoid the use of NSAIDs in?

A

i. Older adults (>65)
ii. Renal insufficiency
iii. Uncontrolled hypertension
iv. History of GI bleed
v. CV disease

23
Q

Colchicine

A
  • Interference with migration of neutrophils to sites of inflammation that have been induced by deposits of monosodium urate crystals in synovial fluid
  • 1st day: 1.2 mg initially, than 0.6 mg one hour later; day 2 and thereafter 0.6 mg twice daily until flare resolves
  • Should start within 36 hours of attack
    • If using for prophylaxis, start 12 hours after 2nd dose
      0.6 mg once daily or BID
24
Q

What are the side effects of colchicine?

A

i. N/V
ii. Diarrhea
iii. Abdominal pain
iv. Muscle pain or weakness

25
Q

Dosage of Prednisone

A

30-40 mg/day until resolution of attack, then taper by 5 mg each day for 7-10 days

26
Q

What is the dosage for methylprednisolone?

A

Medrol dose pack
* 1. 21-day regimen

27
Q

Intraarticular corticosteroid injections

A
  • Triamcinolone 10 mg, 30 mg, or 40 mg
  • Dose based on size of joint (small, medium, or large)
  • 1-2 joints
28
Q

IM Triamcinolone

A

i. 60 mg followed by oral corticosteroid
ii. If multiple joints

29
Q

Intercritical gout

A
  • Asymptomatic period between attacks
  • Patients may experience
  • Persistent urate crystals in joint
  • Low-grade chronic inflammation
30
Q

Chronic gout is indicated if ANY of the following:

A
  • ≥ 1 subcutaneous tophi
  • ≥ 2 attacks per year (frequent)
  • Evidence of radiographic damage
31
Q

What is the first line treatment for chronic gout?

A

Xanthine oxidase inhibitors (XOI)
1. Allopurinol first line agent for all patients
2. Alternative: Febuxostat

32
Q

What is an alternative first-line for chronic gout?

A

Alternative First line: Probenicid
1. A uricosuric if at least one XOI is contraindicate or not tolerated

33
Q

Lesinurad

A

-add on therapy for chronic gout
-selective uric acid reabsorption inhibitor
-only as add on to allopurinol or febuxostat
-MOA: Inhibits the function of renal apical transporters that facilitate reabsorption of uric acid

34
Q

What is the dosing for Allopurinol?

A

What * Starting dose: 100 mg/day
- If CrCl < 60 mL/min–> 50 mg/day
* Increase 50-100 mg/day every 4 weeks
- Target uric acid level < 6 mg/dL (max 800 mg)
* Slow dose titrations reduce the risk of gout flares during initiation

35
Q

What do you monitor for allopurinol?

A

i. Rash, diarrhea, nausea, elevations in LFTs, neutropenia

36
Q

Allopurinol Hypersensitivity Syndrome

A
  • Concern for TEN and SJS (potentially fatal)
  • Han Chinese, Tai, or Korean at increased risk
  • Prior to initiating, HLA testing (HLA-B*5801) should be considered for those at high risk of hypersensitivity
37
Q

What is the dosing for Fubxostat?

A
  • Dosing: 40mg once daily
  • If uric acid still > 6 mg/dL after ≥ 2 weeks, increase 80 mg once daily
38
Q

What are some clinical pearls for Febuxostat?

A

i. More costly than allopurinol
ii. Caution with ischemic heart disease or CHF
iii. Monitor LFTs

39
Q

Probenicid

A
  1. A uricosuric if at least one XOI is contraindicate or not tolerated
  2. MOA: Inhibits tubular urate reabsorption in kidneys
40
Q

What is dosing of Probenicid?

A

a. 250 mg po BID
b. Increase q4 weeks to max 1000 mg bid until goal urate serum

41
Q

What are some contraindications of Probenicid?

A

a. History of urolithiasis, can increase risk of kidney stones
- Counsel to INCREASE FLUID intake at least when initiating (prevent kidney stones)
b. CrCl < 50 mL/min
c. Increased urinary uric acid

42
Q

What is the dosing of Lesinurad?

A

a. 200 mg once daily with food, water and XOI
b. Leisinurad 200 mg/allopurinol 200 mg or 300 mg (Duzallo)

43
Q

What are some contraindications of Lesinurad?

A

a. CrCl < 45 mL/min
b. Monitor Scr

44
Q

When do you use Pegloticase (Krystexxa)?

A
  • Last line
  • If goal of SU < 6 mg/dL not achieved, discontinue other therapies and change to pegloticase
    • ONLY if gout disease burden is severe and refractory/intolerant to other options
  • Dosing: 8 mg IV every 2 weeks

Adv. Immunology (3 decks)

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